Cancer will affect 1 out of 2 men and 1 out of 3 women in their lifetime and is among one of the leading causes of death in the United State. Millions of dollars and hours are spent each year to find a cure, and yet cancer treatments continue to be less effective than desired. Treatments that involve radiation and toxic drugs often leave survivors with devastating side effects. This project will seek to provide an alternative treatment option for cancer patients that will have fewer short and long term side effects. The promising cancer treatment addressed by this project involves the utilization of the host immune system to combat existing cancers and possibly prevent new cancers. Currently it is known that the immune system has the potential to either inhibit or promote the growth of solid tumors by creating a tumor microenvironment that inhibit or promotes tumor growth. A greater understanding of these mechanisms is needed in order to successfully modulate the immune system to target cancer cells for destruction. To study how microRNA, a novel class of regulatory RNA, can be modulated within the immune system to promote better immune responses against tumors, the following aims will be addressed: 1) Determine the immunological role of miR-155 during de novo primary tumor formation and immunoediting, 2) Determine the immunological role of miR-155 during lung tumor metastasis. These aims will address the hypothesis that MicroRNA- 155 plays a protective role during the formation of solid tumors by directing a competent immune response against de novo tumor formation and metastasizing tumor cells. Well- established genetic and carcinogenic models of tumor formation will be used to study the utility of microRNA modulation within the immune system in an effort to treat and prevent cancer. Upon its completion, this study will advance the field of cancer immunology. It will also improve the lives of cancer patients by increasing the ability of the medical community to modulate the immune system to fight cancers specifically with fewer harmful side effects.